Thongpon Phonpilas, Tang Menghuan, Cong Zhaoqing
Department of Biochemistry & Molecular Medicine, University of California Davis, Sacramento, CA 95817, USA.
South China Hospital, Medical School, Shenzhen University, Shenzhen 518116, China.
Biomedicines. 2025 Jun 9;13(6):1415. doi: 10.3390/biomedicines13061415.
Cancer treatment continues to face significant challenges due to the limitations of conventional therapies, including non-specific toxicity, poor bioavailability, and drug resistance. Nanotechnology, particularly peptide-based nanoparticles (NPs), is increasingly recognized as a valuable strategy to address these obstacles. Peptides provide a versatile platform offering high biocompatibility, specificity, biodegradability, and minimal immunogenicity, making them ideal for targeted cancer therapies. This review comprehensively examines recent advancements in peptide-based nanoparticle systems, highlighting the mechanisms driving peptide self-assembly, such as amphiphilicity, non-covalent interactions, and metal coordination. It distinguishes between non-bioactive peptide nanoparticles, which primarily serve as drug carriers, and bioactive peptide nanoparticles, which integrate targeting peptides, cell-penetrating peptides (CPPs), and therapeutic peptides to enhance specificity, internalization, and anticancer efficacy. Emphasis is placed on innovative designs that exploit active targeting, stimuli-responsive release, and immunomodulatory strategies to maximize therapeutic outcomes while minimizing side effects. Despite promising preclinical outcomes, the clinical translation of peptide nanoparticles struggles with challenges involving stability, delivery efficiency, scalability, regulatory compliance, and manufacturing complexity. The review concludes by outlining future directions, emphasizing personalized nanomedicine, combination therapies, and advanced peptide engineering as crucial pathways toward successful clinical implementation.
由于传统疗法存在局限性,包括非特异性毒性、生物利用度差和耐药性,癌症治疗仍然面临重大挑战。纳米技术,特别是基于肽的纳米颗粒(NPs),越来越被认为是解决这些障碍的一种有价值的策略。肽提供了一个多功能平台,具有高生物相容性、特异性、可生物降解性和最小免疫原性,使其成为靶向癌症治疗的理想选择。本文综述全面考察了基于肽的纳米颗粒系统的最新进展,突出了驱动肽自组装的机制,如两亲性、非共价相互作用和金属配位。它区分了主要作为药物载体的非生物活性肽纳米颗粒和整合靶向肽、细胞穿透肽(CPPs)和治疗肽以增强特异性、内化和抗癌疗效的生物活性肽纳米颗粒。重点介绍了利用主动靶向、刺激响应释放和免疫调节策略的创新设计,以在最小化副作用的同时最大化治疗效果。尽管临床前结果很有前景,但肽纳米颗粒的临床转化仍面临稳定性、递送效率、可扩展性、法规合规性和制造复杂性等挑战。综述最后概述了未来方向,强调个性化纳米医学、联合疗法和先进的肽工程是成功临床应用的关键途径。